US2020048347A1PendingUtilityA1
Bispecific antibodies
Est. expirySep 1, 2036(~10.1 yrs left)· nominal 20-yr term from priority
C07K 16/244C07K 2317/73C07K 16/2803C07K 16/2887C07K 2317/24C07K 16/22A61K 2039/505C07K 16/2809C07K 16/468C07K 2317/31C07K 16/303A61P 35/00C07K 16/30
42
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
In certain aspects, bispecific antibodies and uses thereof are provided.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A bispecific antibody represented by structural formula (II): wherein: LCA is a light chain antibody portion: HCA is a heavy chain antibody portion; LCB is a light chain antibody portion; HCB is a heavy chain antibody portion; L 1 , L 2 and L 3 include
wherein:
Y 1 is O (oxygen), NR 4 , —NH—NH—, or —CH═CH—;
Y 2 is OH or C 1-6 alkoxy;
Y 3 is O (oxygen), N—OR 4 , or —CF 2 —;
Y 4 is O (oxygen), N—OR 4 , or —CF 2 —;
R 1 is H (hydrogen), C 1-6 alkyl, aryl, or heteroaryl;
R 2 is H (hydrogen) or C 1-6 alkyl;
R 3 is H (hydrogen) or C 1-6 alkyl; and
R 4 is H (hydrogen) or C 1-6 alkyl,
wherein LCA and LCB are not derived from the same antibody.
2 . The bispecific antibody of claim 1 , wherein HCA includes a heavy chain portion from IgA, IgD, IgE, IgG, or IgM, or up to 10 amino acid replacement sequence thereof or chimera thereof.
3 . The bispecific antibody of claim 1 or 2 , wherein HCB includes a heavy chain portion from IgA, IgD, IgE, IgG, or IgM, or up to 10 amino acid replacement sequence thereof or chimera thereof.
4 . The bispecific antibody of any one of claims 1 to 3 , wherein LCA includes a light chain portion from IgA, IgD, IgE, IgG, or IgM, or up to 10 amino acid replacement sequence thereof or chimera thereof.
5 . The bispecific antibody of any one of claims 1 to 3 , wherein LCB includes a light chain amino portion from IgA, IgD, IgE, IgG, or IgM, or up to 10 amino acid replacement sequence thereof or chimera thereof.
6 . The bispecific antibody of any one of claims 1 to 5 , wherein LCA, LCB, HCA and HCB each comprise at least one modified L-cysteine-amino acid residue having a carbon-sulfur-carbon bond.
7 . The bispecific antibody of any one of claims 1 to 5 , wherein at least one sulfur of —S-L 1 -S—, —S-L 2 -S—, or —S-L 3 -S— is from an L-Cysteine of a peptide before conjugation.
8 . The bispecific antibody of any one of claims 1 to 5 , wherein —S-L 1 -S—, —S-L 2 -S—, or —S-L 3 -S— comprise at least one thioether.
9 . The bispecific antibody of any one of claims 1 to 5 , wherein L 1 , L 2 or L 3 includes a 2-carbon bridge, 3-carbon bridge, or 4-carbon bridge.
10 . The bispecific antibody of any one of claim 8 or 9 , wherein —S-L 1 -S—, —S-L 2 -S—, or —S-L 3 -S— includes a fragment selected from the group consisting of:
11 . The bispecific antibody of any one of claims 1 to 10 , wherein HCA and HCB each include the amino acid sequence SPPC, CPPS, APPC or CPPA in the hinge region wherein the cysteine sulfur of the SPPC, CPPS, APPC or CPPA sequence of HCA and HCB is covalently bonded to L 3 , wherein LCA and LCB are not derived from the same antibody.
12 . The bispecific antibody of any one of claims 1 to 11 , wherein at least one amino acid residue in the hinge region of HCA or HCB is replaced with at least one cysteine residue.
13 . The bispecific antibody of any one of claims 1 to 11 , wherein at least one amino acid residue in the hinge region of HCA and HCB is replaced with at least one cysteine residue.
14 . The bispecific antibody of claim 12 or 13 , wherein at least two amino acid residues in the hinge region of HCA and HCB are each replaced with a cysteine residue.
15 . The bispecific antibody of any one of claims 12 to 14 , wherein at the hinge region of HCA and/or HCB comprises amino acids 210-250 (EU numbering system).
16 . The bispecific antibody of any one of claims 12 to 14 , wherein at the hinge region of HCA and/or HCB consists of amino acids 210-250 (EU numbering system).
17 . A method of making the bispecific antibody of any one of claims 1 to 16 comprising:
treating
with X-L-X for a period of time to provide the bispecific antibody,
wherein X is halo or —OS(O) 2 —R 6 ;
L is
Y 1 is O (oxygen), NR 4 , —NH—NH—, or —CH═CH—;
Y 2 is OH or C 1-6 alkoxy;
Y 3 is O (oxygen), N—OR 4 , or —CF 2 —;
Y 4 is O (oxygen), N—OR 4 , or —CF 2 —;
R 1 is H (hydrogen), C 1-6 alkyl, aryl, or heteroaryl;
R 2 is H (hydrogen) or C 1-6 alkyl;
R 3 is H (hydrogen) or C 1-6 alkyl;
R 4 is H (hydrogen) or C 1-6 alkyl; and
R 6 is a synthetic linker optionally substituted C 1-6 alkyl, optionally substituted aryl or optionally substituted heteroaryl.
18 . The method claim 17 , wherein HCA includes a heavy chain portion from IgA, IgD, IgE, IgG, or IgM, or up to 10 amino acid replacement sequence thereof or chimera thereof.
19 . The method of claim 17 or 18 , wherein HCB includes a heavy chain portion from IgA, IgD, IgE, IgG, or IgM, or up to 10 amino acid replacement sequence thereof or chimera thereof.
20 . The method of any one of claims 17 to 19 , wherein LCA includes a light chain portion from IgA, IgD, IgE, IgG, or IgM, or up to 10 amino acid replacement sequence thereof or chimera thereof.
21 . The method of any one of claims 17 to 20 , wherein LCB includes a light chain portion from IgA, IgD, IgE, IgG, or IgM, or up to 10 amino acid replacement sequence thereof or chimera thereof.
22 . The method of any one of claims 17 to 21 , wherein LCA, LCB, HCA and HCB each comprise at least one modified L-cysteine-amino acid residue having a carbon-sulfur-carbon bond.
23 . The method of any one of claims 17 to 22 , wherein at least one sulfur of —S-L 3 -S— is from an L-Cysteine of a peptide before covalently bonding to the linker.
24 . The method of any one of claims 17 to 22 , wherein —S-L 1 -S—, —S-L 2 -S—, or —S-L 3 -S— comprise at least one thioether.
25 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSA
ITWNSGHIDYADSVEGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKVS
YLSTASSLDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP
VLDSDGSFLLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS
PGK.
26 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVGW
INTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKYP
HYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
TQTYICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFP
PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYDGVEVHNAKTKPREEQ
YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP
PVLDSDGSFLLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP
GK.
27 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
QVQLVQSGAEVKKPGSSVKVSCKASGYSFTDYHIHWVRQAPGQGLEWMGV
INPMYGTTDYNQRFKGRVTITADESTSTAYMELSSLRSEDTAVYYCARYD
YFTGTGVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
ICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV
YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.
28 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMNWVRQAPGKGLEWVAA
INQDGSEKYYVGSVKGRFTISRDNAKNSLYLQMNSLRVEDTAVYYCVRDY
YDILTDYYIHYWYFDLWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
SSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS
LSLSPGK.
29 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSY
ISDDGSLKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKHP
YWYGGQLDLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVKTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEVKCKVSNKALPAPIEKTISKAKGQPREPQ
VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
K.
30 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
QVQLVESGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMG
WINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARS
PNPYYYDSSGYYYPGAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSG
GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP
ENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYT
QKSLSLSPGK.
31 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
QVQLQESGPGLVKPSETLSLTCTVSGGSISIYYWSWIRQPPGKGLEWIGY
VYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLNSVTAADTAVYYCARGGY
DFWSGYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGYEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ
VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
K.
32 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
QVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHWVRQAPGQGLEWMGY
INPRSGYTHYNQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCARSA
YYDYDGFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ
VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFLLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
K.
33 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGA
IYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARST
YYGGDWYFNVWGAGTTVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP
VLDSDGSFFLYSRLTVDKSRWQQGNYFSCSVMHEALHNHYTQKSLSLSPG
K.
34 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAASGFDLGFYFYACWVRQAPGKGLEWVS
CIYTAGSGSTYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
STANTRSTYYLNLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLF
PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRE
EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL
SPGK.
35 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
EVQLVESGGGLVKPGGSLRLSCAASGFTFSGYGMSWVRQAPGKGLEWVSS
ITSGGTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSL
AGNAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI
CNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTTSKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFLLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.
36 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
QVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSY
ISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAREM
QFGWELLGAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
TQTYICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFP
PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE
QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT
PPVLDSDGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS
PGK.
37 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAASGFTFNNYAMSWVRQAPGKGLEWVST
ISSDGTYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHP
PSYYYAFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLVSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ
VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
K.
38 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAASGFTFNNAMSWVRQAPGKGLEWVSTI
SSDGTYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHPP
SYYYAFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
ICNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV
YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.
39 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAASGFTFNKNAMNWVRQAPGKGLEWVAR
IRNKTNNYATYYAASVKGRFTISRDDSKSSLYLQMNNLKTEDTAMYYCVA
GNSFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.
40 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
QVQLQESGPGLVKPSETLSLTCVVSGGSISSSNWWSWVRQPPGKGLEWIG
EIYHSGSPDYNPSLKSRVTISVDKSRNQFSLKLSSVTAADTAVYYCAKVS
TGGFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI
CNVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.
41 . The bispecific antibody or method of any one of claims 1 to 24 , wherein HCA and/or HCB include the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAASGFTFNKNAMNWVRQAPGKGLEWVAR
IRNKTNNYATYYAASVKGRFTISRDDSKSSLYLQMNNLKTEDTAMYYCVA
GNSFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKRVEPKSCDKTHTSPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.
42 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIY
GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPCTFG
QGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ
GLSSPVTKSFNRGEC.
43 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYF
TSSLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQ
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNFYPREAKVQWKVD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL
SSPVTKSFNRGEC.
44 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
DIVMTQTPLSLSVTPGQPASISCRSSRSLVHSRGNTYLHWYLQKPGQSPQ
LLIYKVSNRFIGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTHLP
FTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK
VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE
VTHQGLSSPVTKSFNRGEC.
45 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIY
GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPCTFG
QGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ
GLSSPVTKSFNRGEC.
46 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
SYELTQPPSVSVSPGQTASITCSGDSLGSYFVHWYQQKPGQSPVLVIYDD
SNRPSGIPERFSGSNSGNTATLTTSGTQAMDEADYYCSAFTHNSDVFGGG
TKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKA
DSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGS
TVEKTVAPTECS.
47 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
QPGLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDD
SDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHYVFG
TGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAW
KADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHE
GSTVEKTVAPTECS.
48 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
EIVMTQSPATLSVSPGERATLSCRASQSVDSNLAWYRQKPGQAPRLLIYG
ASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYINWPPITFG
QGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ
GLSSPVTKSFNRGEC.
49 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
DIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQKPGKAPKRLIYDT
SKLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSSNPPTFGGG
TKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL
SSPVTKSFNRGEC.
50 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYAT
SNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSPPTFGGGT
KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN
ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS
SPVTKSFNRGEC.
51 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYA
ASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTFGQ
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC.
52 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
DIQMTQSPSSLSASVGDRVTITCQASQRISSYLSWYQQKPGKVPKLLIYG
ASTLASGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQSYAYFDSNNWH
AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV
QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEV
THQGLSSPVTKSFNRGEC.
53 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
EIVLTQSPDFQSVTPKEKVTITCRASQTISDYLHWYQQKPDQSPKLLIKF
ASQSFSGVPSRFSGSGSGTDFTLTINSLEAEDAATYYCQNGHGFPRTFGQ
GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC.
54 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
EIVLTQSPGTLSLSPGERATLSCRASESVDSYGNSFIHWYQQKPGQAPRL
LIYLASNLESGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQNNEDLW
TFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV
QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEV
THQGLSSPVTKSFNRGEC.
55 . The bispecific antibody or method of any one of claims 1 to 24 , wherein LCA and/or LCB include the amino acid sequence:
DIVMTQSPSSLAVSLGERVTMTCKSSQSLLYSSNQKNYLAVVYQQKPGQS
PKLLIYWASSRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYN
YPLTFGQGTRLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA
CEVTHQGLSSPVTKSFNRGEC.
56 . The bispecific antibody of any one of the preceding claims, wherein bispecific antibody targets EGFR/Her2, Her2/Her3, EGFR/cMet, CTLA-4/PD-1, PD-1/TIM-3, PD-1/LAG-3, PD-1/KIR, PD-1/NKD2A, PD-L1/CD47, CD3-CD19, CD3-CD20, CD3-CD33, CD3-CD123, CD3-CD38, NKG2D-Trop2, NKG2D-5T4, NKG2D-GPC3, NKG2D-Mesothelin, NKG2D-WT1, NKG2D/NY-ESO, NKp46-Trop2, NKp46-5T4, NKp46-GPC3, NKp46-Mesothelin, NKp46-WT1, NKp46-ESO, CD47-CD22, CD47-CD33, CD47-CD123, CD3-CD38, CD47-Trop2, CD47-5T4, CD47-GPC3, CD47-Mesothelin, CD47-WT1, or CD47-ESO.
57 . The bispecific antibody of any one of claims 42 - 56 , wherein LCA and/or LCB include an amino acid sequence that is at least 90° % identical to that of the recited amino acid sequence.
58 . The bispecific antibody of any one of claims 25 - 41 , wherein HCA and/or HCB include an amino acid sequence that is at least 90% identical to that of the recited amino acid sequence.
59 . A method of treating cancer, comprising administering a bispecific antibody according to any one of claims 1 - 58 to a subject in need thereof, wherein the cancer is selected from the group consisting of a carcinoma, a sarcoma, a lymphoma, and a blastoma.
60 . A method of treating cancer, comprising administering a bispecific antibody according to any one of claims 1 - 58 to a subject in need thereof, wherein the cancer is selected from the group consisting of uterine sarcoma cancer, bladder cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, lung cancer, melanoma, non-Hodgkin lymphoma, glioblastoma, pancreatic cancer, prostate cancer, ovarian cancer, and thyroid cancer.
61 . A method of treating a disease selected from the group consisting of uterine sarcoma cancer, bladder cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, lung cancer, melanoma, non-Hodgkin lymphoma, leukemia, pancreatic cancer, prostate cancer, ovarian cancer, and thyroid cancer, comprising administering a bispecific antibody according to any one of claims 1 - 58 to a subject in need thereof.
62 . A method of delivering a bispecific antibody according to any one of claims 1 - 56 to an in vivo mammalian cell, the method comprising administering a compound of any one of claims 1 - 58 to a mammal comprising the in vivo mammalian cell.
63 . The method of claim 62 , wherein the compound is administered parenterally.
64 . The method of claim 63 , wherein the compound is administered intravenously.
65 . The method of claim 62 , wherein the compound is administered orally.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.